Editor's Comment: Serotonin (5-HT) is a neurotransmitter found primarily in the brain and gut. In the brain, serotonin serves a variety of functions, among which are regulating sleep, appetite, and mood. However, roughly 90% of serotonin is found in the gut, where it serves to regulate intestinal contractions. The importance of this study is that it showed that autoimmunity against serotonin not only correlates with ME/CFS symptoms, but that it can be caused by inflammation due to the translocation of intestinal flora (bacteria) across the gut membrane. The role of the gut (e.g. alterations in flora and increased permeability of the intestinal lining) in chronic disease states is increasingly a subject of interest in the medical research community.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation.

Methods: We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF) alpha, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale).

Results: The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNF alpha, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise.

Discussion: The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder.

Further support of the involvement of serotonin in fibromyalgia is that one of serotonin's conversion end products, melatonin, was found to be elevated in patients with fibromylagia (discussed at http://www.supplements-and-health.com/tryptophan-side-effects.html ). Serotonin is a basic inflammatory chemical, not a "happy chemical" as the medical propaganda portrays the substance to the public.